Nonconventional chemical inhibitors of microRNA: therapeutic scope

2015 ◽  
Vol 51 (5) ◽  
pp. 820-831 ◽  
Author(s):  
Gopal Gunanathan Jayaraj ◽  
Smita Nahar ◽  
Souvik Maiti

MicroRNAs (miRNAs) are a class of genomically encoded small RNA molecules (∼22nts in length), which regulate gene expression post transcriptionally. miRNAs are implicated in several diseases, thus modulation of miRNA is of prime importance. Small molecules offer a non-conventional alternative to do so.

2020 ◽  
Vol 19 (03) ◽  
pp. 2040001 ◽  
Author(s):  
Ting Zhou ◽  
Huiwen Wang ◽  
Linlu Song ◽  
Yunjie Zhao

Riboswitch can bind small molecules to regulate gene expression. Unlike other RNAs, riboswitch relies on its conformational switching for regulation. However, the understanding of the switching mechanism is still limited. Here, we focussed on the add A-riboswitch to illustrate the dynamical switching mechanism as an example. We performed molecular dynamics simulation, conservation and co-evolution calculations to infer the dynamical motions and evolutionary base pairings. The results suggest that the binding domain is stable for molecule recognition and binding, whereas the switching base pairings are co-evolutionary for translation. The understanding of the add A-riboswitch switching mechanism provides a potential solution for riboswitch drug design.


2006 ◽  
Vol 6 ◽  
pp. 1828-1840 ◽  
Author(s):  
Danielle Maatouk ◽  
Brian D. Harfe

Over 10 years ago, the lab of Victor Ambros cloned an unusual gene,lin-4, which encodes two small RNA transcripts[1]. In the past few years, hundreds more of these tiny transcripts, termed microRNAs (miRNAs), have been uncovered in over a dozen species. The functions of the first two miRNAs,lin-4andlet-7, were relatively easy to identify since they were found in forward genetic screens in Caenorhabditis elegans[1,2,3]. However, uncovering the functions of the growing list of miRNAs presents a challenge to developmental biologists. This review will describe our current understanding of how miRNAs regulate gene expression and will focus on the roles these noncoding RNAs play during the development of both invertebrate and vertebrate species.


2018 ◽  
Vol 2 (2) ◽  
pp. 499-505
Author(s):  
Ignacio Roa

MicroRNAs (miRNAs) are a class of small RNA molecules noncoding to proteins, which regulate gene expression at post-transcriptional level by binding to specific sequences within target genes. miRNAs have been recognized as important regulatory factors in the body development and expression of certain diseases. Some miRNAs regulate the proliferation and differentiation of cells and tissues during odontogenesis.


2021 ◽  
Author(s):  
Colin Kenny ◽  
Ramile Dilshat ◽  
Hannah Seberg ◽  
Eric Van Otterloo ◽  
Gregory Bonde ◽  
...  

Transcription factors in the Activating-enhancer-binding Protein 2 (TFAP2) family redundantly regulate gene expression in melanocytes and melanoma. Previous ChIP-seq experiments indicate that TFAP2A and Microphthalmia-associated Transcription Factor (MITF), a master regulator in these cell types, co-activate enhancers of genes promoting pigmentation. Evidence that TFAP2 paralogs can serve as pioneer factors supports the possibility that TFAP2 facilitates MITF binding at co-bound enhancers, although this model has not been tested. In addition, while MITF and TFAP2 paralogs both appear to repress genes that promote invasion, whether they do so by co-repressing enhancers is unknown. To address these questions we evaluated gene expression, chromatin accessibility, TFAP2A and MITF binding, and chromatin marks characteristic of active enhancers in SK-MEL-28 melanoma cells that were wild-type or deleted of the two TFAP2 paralogs with highest expression, TFAP2A and TFAP2C (i.e., TFAP2-KO cells). Integrated analyses revealed distinct subsets of enhancers bound by TFAP2A in WT cells that are inactivated and activated, respectively, in TFAP2-KO cells. At enhancers bound by both MITF and TFAP2A, MITF is generally lost in TFAP2A/TFAP2C double mutants, but not vice versa, implying TFAP2 pioneers chromatin access for MITF. There is a strong correlation between the sets of genes inhibited by MITF and TFAP2, although we did not find evidence that TFAP2 and MITF inhibit enhancers cooperatively. The findings imply that MITF and TFAP2 paralogs cooperatively affect the melanoma phenotype.


2011 ◽  
Vol 2 (3) ◽  
pp. 127-134
Author(s):  
Tiia Husso ◽  
Mikko P. Turunen ◽  
Nigel Parker ◽  
Seppo Ylä-Herttuala

AbstractSmall RNAs have been shown to regulate gene transcription by interacting with the promoter region and modifying the histone code. The exact mechanism of function is still unclear but the feasibility to activate or repress endogenous gene expression with small RNA molecules has already been demonstrated in vitro and in vivo. In traditional gene therapy non-mutated or otherwise useful genes are inserted into patient's cells to treat a disease. In epigenetherapy the action of small RNAs is utilized by delivering only the small RNAs to patient's cells where they then regulate gene expression by epigenetic mechanisms. This method could be widely useful not only for basic research but also for clinical applications of small RNAs.


MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Rebecca Mathew ◽  
Valentina Mattei ◽  
Muna Al Hashmi ◽  
Sara Tomei

MicroRNAs are RNA molecules of ~22 nt length that regulate gene expression posttranscriptionally. The role of miRNAs has been reported in many cellular processes including apoptosis, cell differentiation, development and proliferation. The dysregulated expression of miRNAs has been proposed as a biomarker for the diagnosis, onset and prognosis of human diseases. The utility of miRNA profiles to identify and discriminate patients from healthy individuals is highly dependent on the sensitivity and specificity of the technologies used for their detection and the quantity and quality of starting material. In this review, we present an update of the current technologies for the extraction, QC assessment and detection of miRNAs with special focus to the most recent methods, discussing their advantages as well as their shortcomings.


2020 ◽  
Vol 21 (4) ◽  
pp. 1270 ◽  
Author(s):  
Antonella Fioravanti ◽  
Luigi Pirtoli ◽  
Antonio Giordano ◽  
Francesco Dotta

MicroRNAs (miRNA), are short regulatory RNA molecules that regulate gene expression by binding specific sequences within target messenger RNA (mRNA) [...]


2021 ◽  
Vol 12 ◽  
Author(s):  
Junjian He ◽  
Xiaoxin Ma

Long non-coding RNAs (LncRNAs) can bind to other proteins or RNAs to regulate gene expression, and its role in tumors has been extensively studied. A common RNA binding protein, UPF1, is also a key factor in a variety of RNA decay pathways. RNA decay pathways serve to control levels of particular RNA molecules. The expression of UPF1 is often dysregulated in tumors, an observation which suggests that UPF1 contributes to development of a variety of tumors. Herein, we review evidence from studies of fourteen lncRNAs interact with UPF1. The interaction between lncRNA and UPFI provide fundamental basis for cell transformation and tumorigenic growth.


Neurotrauma ◽  
2018 ◽  
pp. 261-268
Author(s):  
Manish Bhomia ◽  
Nagaraja S. Balakathiresan ◽  
Kevin K. W. Wang ◽  
Barbara Knollmann-Ritschel

Traumatic brain injury (TBI) is currently considered one of the major causes of disability and death worldwide. The cellular and molecular changes of TBI pathology are dynamic and complex in nature. MicroRNAs (miRNA) are small endogenous RNA molecules that regulate gene expression at the posttranscriptional level. Several studies have shown a critical role of miRNAs in the development of long- and short-term TBI pathology. Circulating miRNAs are of great interest as blood-based biomarkers in TBI diagnosis. In this chapter, the authors review recent reports that aim to understand the role of miRNAs in TBI pathophysiology and their potential use as a therapeutic target. Additionally, the authors discuss the potential use of miRNAs as blood-based diagnostic markers for TBI and their possible association with other neurodegenerative diseases.


mBio ◽  
2011 ◽  
Vol 2 (5) ◽  
Author(s):  
Christopher M. Johnson ◽  
Heather H. A. Haemig ◽  
Anushree Chatterjee ◽  
Hu Wei-Shou ◽  
Keith E. Weaver ◽  
...  

ABSTRACTIn bacteria, RNAs regulate gene expression and function via several mechanisms. An RNA may pair with complementary sequences in a target RNA to impact transcription, translation, or degradation of the target. Control of conjugation of pCF10, a pheromone response plasmid ofEnterococcus faecalis, is a well-characterized system that serves as a model for the regulation of gene expression in bacteria by intercellular signaling. TheprgQoperon, whose products mediate conjugation, is negatively regulated by two products of theprgXoperon, Anti-Q, a small RNA, and PrgX, the transcriptional repressor of theprgQpromoter. Here we show that Qs, an RNA from the 5′ end of theprgQoperon, represses expression of PrgX by targetingprgXmRNA for cleavage by RNase III. Our results demonstrate that theprgQandprgXoperons each use RNAs to negatively regulate gene expression from the opposing operon by different mechanisms. Such reciprocal regulation between two operons using RNAs has not been previously demonstrated. Furthermore, these results show that Qs is an unusually versatile RNA, serving three separate functions in the regulation of conjugation. Understanding the potential versatility of RNAs and their various roles in gene regulatory networks will allow us to better understand how cells regulate complex behavior.IMPORTANCEBacteria use RNA to regulate gene expression by a variety of mechanisms. TheprgQandprgXoperons of pCF10, a conjugative plasmid ofEnterococcus faecalis, have been shown to negatively regulate one another by a variety of mechanisms. One of these mechanisms involves Anti-Q, a small RNA from theprgXoperon that prevents gene expression from theprgQoperon. In this work, we find that Qs, an RNA from theprgQoperon, negatively regulates gene expression from theprgXoperon. These findings have a number of implications. (i) The Anti-Q and Qs RNAs act by different mechanisms, highlighting the variety of ways in which bacteria can regulate gene expression using RNAs. (ii) Reciprocal regulation between operons mediated by small RNAs has not been previously described, deepening our understanding of how bacteria regulate complex behavior. (iii) Additional roles for Qs have been described, demonstrating the versatility of this RNA.


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